Health

It's a fact: malaria kills over a million people a year and stands in the way of economic development for many countries where the disease is endemic. Past efforts to eradicate this deadly disease with drug treatments like quinine, chloriquine, and other antimalarials have proven futile as the malaria parasite (Plasmodium Falciparum) has developed resistance to these drugs. However, artemisinin, with no known stable resistance, has been ganarring momentous support from both the non-profit and for-profit sectors as the first line drug treatment for uncomplicated and multi-drug resistant P. Falciparum malaria.
Currently, according to the World Health Organization, since 2001, a total of 56 countries have adopted one of the WHO recommended artemisinin-based combination therapies, several as first-line treatment and a few as second-line. With this increasing use of Artemisinin comes the threat of the malaria parasite developing resistance to the drug. There is a growing concern in the field of malaria therapy that if or when the parasite develops resistance to artemisinin, like it has done with other antimalarials, no one will know how to combat the resistance because the mechanism of action of artemisinin is uncertain.
There are two strong competing hypothesis as to how the drug actually kills the parasite. One hypothesis, the multiple targets hypothesis, contends that artemisinin kills the parasite by reacting with the iron in hemin to produce oxygen radicals. The other hypothesis argues that artemisinin acts via a specific protein. My research this past summer was focused on using novel protocols in proteomics to find the protein target(s) of artemisnin, with hopes of disproving one of these two hypothesis. The results I obtained from my protein gels at the end were inconclusive and further experiments are needed to clarify my data.

Characterization of the FlpA Protein and Its Role in Flagellar Placement and Pathogenesis of Pseudomonas aeruginosa

Organization/Location:

Princeton University

Adviser(s):

Zemer Gitai

Over the summer I worked with the bacteria Pseudomonas aeruginosa in the Gitai lab in Princeton, NJ. P. aeruginosa is a gram-negative bacteria that infects immune-challenged humans as well as many model organisms such as C. elegans. It is most dangerous to humans with cystic fibrosis and severe burn victims. To infect, P. aeruginosa uses flagella, a propeller-like tail, and type IV pili, a shorter structure that functions somewhat like a grappling hook. After initial infection, P. aeruginosa forms biofilms for better growth and increased antibiotic resistance. If the flagella or pili are mislocalized, meaning they are not placed at one of the poles of the bacteria, it has been shown the bacterium has reduced infection strength.
The previous student in the lab where I worked, Natsai Nyakudarika, ran a screen for bacteria with transposon-insertion mutations that affected flagellar function. She looked for bacteria defective in swimming motility, followed by checking these mutants for mislocalization of the protein flhF, a protein responsible for localization of the flagella. She discovered a gene she named flagellar localizing protein A (flpA) that had two mutations responsible for irregular flagellar placement. My goal was to ascertain the role of flpA in flagellar localization.
In the course of my research, I discovered that multiple genes may be responsible for the defect in flagellar placement. My current focus is to identify which genes direct flagellar placement, how they direct flagellar placement, and what their importance in virulence is. I plan on using the C. elegans organism to determine the virulence levels of mutant P. aeruginosa.

Water quality is a serious issue in Nigeria, and many communities, both urban and rural, do not have access to potable water. After two years of preliminary research, Prof. Soboyejo and a group of 4 students traveled to Abeokuta with two goals: to start a ceramic water filter factory and to survey a community to begin a study on the impact of the filter. We chose to use the Potters for Peace ceramic filter model because it is effective and produced locally with local materials, clay and sawdust. When firing the ceramic filter, the sawdust burns out and leaves behind a network of fine pores. Reinforced by absorption of a colloidal silver solution that acts as an antiseptic, the filter is effective in removing waterborne bacteria as well as turbidity. In Abeokuta, our team set up a factory by gathering the necessary materials and training a local team. As the factory continues to increase production, we are working to develop an effective marketing plan. We worked in conjunction with the University of Agriculture - Abeokuta and, with the help of local faculty and students, conducted surveys in a village of approximately 50 families to establish their current water situation. With the help of the local students, we will follow this village for the next year to see if the filter has an impact on their health and general quality of life.

I accompanied Professor Biehl on a research trip to Brazil, where in the wake of universal access to AIDS medications, other patients and groups are demanding increased access to a variety of basic and high-cost medications. Following the precedent set by AIDS activists, tens of thousands of patients are suing the government to force it to pay for their medications. They base their claim on the Brazilian constitutional right to health, which they understand as a right to access to pharmaceutical products. The court cases are straining state budgets, disrupting established drug distribution schemes, and raising challenging questions about the right to health, the role of markets and the nature of pharmaceutical access. We are setting up a database to collect information on these cases in southern Brazil, while we engage in a long-term ethnographic project carrying out interviews with members of the judiciary, NGOs and healthcare providers. We aim to understand the meaning and consequences of a right-based administration of health through the judiciary.

"This summer I went to South Africa with three other Princeton students to study local government responses to infectious disease. In today’s globalized world, effective authority is needed to contain the risk of infectious disease, yet the perceptions of and efforts to contain these threats vary across time, space, and infection. Significant variation exists at the national and sub-national levels, and it was our goal as members of “Team Microbe,” to determine potential causes for and implications of these discrepancies across municipalities in South Africa. In order to do this, we designed and conducted a survey of local councilors across two of the country’s nine provinces. By focusing on these two adjacent provinces – the Eastern and Western Capes – we were able to control for “provincial effects,” given the highly similar demographics and socio-economic conditions at their border. We selected our municipalities based on two factors: the degree of racial heterogeneity and the relative strength of political parties. Then, we created categories based on these factors and aimed to include an equal number of municipalities from each group. "
"Over the course of two months, we administered our survey to over 120 officials across fifteen local councils and one “metro” council. Each interview lasted for about an hour and included both open and closed questions that related to each councilor’s policy beliefs, priorities, and personal background. In determining the root causes of these responses, we considered several potential factors of influence, including ethnic/racial identity; international organizations; levels of civil society; strength of institutions (political parties, courts, etc.); as well as cultural attitudes toward the problems themselves. Our project was based out of a rented apartment in Cape Town, though much of our time was spend traveling to outlying municipalities. The logistics of our research were often more complicated than we had anticipated, but we came up with creative solutions and achieved our goals nonetheless. We were especially proud of the information we gathered during our two-week road trip to the Eastern Cape, during which we drove hundreds of miles, interviewed dozens of councilors, and even got to visit a few wildlife preserves."
"Now that the survey is complete and the results have been compiled into a large database, our goal is to find and explicate patterns within it. Each of us is currently working on a thesis or dissertation on a specific component of the survey, and our Professor, Evan Lieberman, will eventually incorporate our study into his own research. As I begin to focus on my own project – a study of policy diffusion among the local governments we surveyed – I realize how much I learned during my summer in South Africa – not just about politics and public health, but about myself and my values, talents, and ambitions. Joining “Team Microbe” was one of the best decisions I’ve made at Princeton, and I have no doubt that I will continue to reflect on and benefit from this experience for a long time to come."

"I had no idea what to expect as I strolled into the Rixile HIV clinic at Tintswalo Hospital in the rural town of Bushbuckridge, South Africa. I certainly didn’t expect an African clinic with 6,000 patients to be run by a scrawny, Scottish doctor in his late twenties. On my first day, I saw more infectious disease than many will see in a lifetime. But just as ubiquitous as the patient’s suffering was the doctor’s constant struggle to provide adequate care. When a doctor had to redo a blood test after the lab lost the previous sample, I was shocked to learn that this was a common occurrence. One mother died in childbirth when a simple blood transfusion would have saved her. The hospital wasn’t out of blood; the nurses simply couldn’t find it. A year after the government purchased the antiretroviral Tenofovir for its treatment regimen, it summarily pulled the plug and failed to issue a plausible explanation. The Scottish doctor told me once that most of his job was spent trying to diagnose TB. The PPD test is useless in immuno-suppressed HIV patients, growing a TB culture takes 40-50 days, the one x-ray machine is constantly broken, and it is nearly impossible to get patients to produce adequate sputum samples."
"But amazingly, the doctors persevered. They would all meet for tea in the morning and discuss difficult cases. X-rays and blood vials made frequent guest appearances. Each day, the HIV clinic doctor squeezed in extra time between his patients to consult on patients in other wards. But most importantly, he treated all of his patients with complete respect, even a traditional healer who was convinced that a rival clan had poisoned her food with HIV. If patients were doing well on treatment, he would down-refer them to local community clinics, for he rightly conceived HIV as a manageable, chronic illness that can be treated on the primary care level. He even helped people secure their disability grants, which was often the biggest concern of many of his patients. Successful treatment regimes were ensured be a variety of social and psychological requirements that complimented the science of treatment. Before starting treatment, each patient had to demonstrate psycho-social preparedness. This included having a “treatment supporter” that could pick up the ARV mediation if the patient were incapacitated and disclosing to one’s partner or family. Each patient also had to attend classes about the ARV drugs and the importance of 100% adherence and meet with a dietician and social worker. This model where laypeople are supporting the scientific community in delivering treatment is the emerging model for successful treatment programs in Africa, and it should undoubtedly be extended elsewhere."
"After my time in the clinic, I spent a month at an economic policy research institute, where I looked into the nature of South Africa’s social welfare system and its effect on HIV patients. I discovered the integral role of the disability grant in the health care system, where patients relied on the grant to finance food and transportation expenses. Unfortunately, HIV patients who begin the ARV treatment regime are losing their grants as their health gets restored by the drugs. Stripping patients of their grant after several months of successful treatment, however, is a paradox of the worst kind. It ignores that patients will still need the same food and transportation security to continue their treatment, which for HIV and other chronic illnesses, is a life-long commitment. With regards to HIV treatment, nutrition is especially essential because malnutrition exacerbates the immunosuppression triggered by HIV. Nutritional deprivation also worsens treatment side effects, which are a main cause of poor adherence. Transportation is equally important for adherence since most patients must travel considerable distances to collect their medication from the hospital. Without drug adherence, drug resistance is inevitable, a phenomenon that will only magnify the HIV epidemic. Since disability grants are not permanent by nature, and since relaxing the eligibility requirements would encourage fraud and distort the labor market, I found that many experts considered it most prudent to address these issues with a basic social grant. A social grant targeted only for those people with HIV would obviously be a stigmatizing nightmare, so the most appropriate solution is a universal, basic income grant."

I conducted a study in Puebla Mexico on how the therapeutic itineraries of HIV/AIDS patients affect their lives. I found that even in the presence of a national plan to distribute medications, stigma remains a huge impediment to treatment and prevention efforts. Doctors assigned by the government to AIDS clinics saw the responsibility as an unwanted burden. Though patients communicated complex fabrics of self-perception, their medical choices were frequently informed by a desire to hide their disease. My research allows for a consideration of how medical and local cultures affect patient and disease conceptions, access to information and the success of treatments.

Radolfzell am Bodensee, Germany
"The money I received through this grant was used to cover the costs of conducting senior thesis research this past summer in Germany. I collaborated with Bryson Voirin, a graduate student at the Max Planck Institute for Ornithology who was conducting a pilot project for what is to be his Ph.D. We shared similar goals in what we wanted to get out of this project, so I had significant liberty in shaping how I wanted the experimental design to look. We also worked closely with Martin Wikelski, former Princeton professor and current director of the Max Planck Institute for Ornithology, in addition to collaborating with researchers at local universities."
"The idea behind the project was to use immuno-compromised chickens as sentinel test animals to assess the spatio-temporal abundances of pathogens in a particular environment. This research was originally going to be conducted in California through UC Davis, but it was moved at the last minute to Germany, where a more accessible facility that would better suit our needs was already in place at the Max Planck Institute. The first goal then, was to determine which environments we would be investigating, as our original plan to disperse chickens all along the western United States coastline to examine latitudinal and altitudinal gradients. In the area of Germany where we were working, the landscape was dominated by vast stretches of farmland with isolated patches of forest scattered throughout. Thus, we decided it would be most interesting and practical to see if we could quantify the degree to which anthropogenic habitat fragmentation affected pathogen dispersal."
"Once the sites were selected, we began to approach the logistical aspects of both compromising the birds’ immune systems, and ways to keep them alive and fully exposed to the environment for five days. There are several established methods for immuno-compromising chickens, and after a thorough literature review and discussions with chicken pathologists, we decided the most effective means would be a bursectomy. This is a procedure in which the bursa of fabricius, an organ responsible for immune responses in birds, is removed from the chickens. We traveled to a medical school in Hungary to learn this obscure procedure, as the next closest scientist who knew how to perform the operation lived in Japan. This minimally invasive procedure was performed on day-old chicks, when the tissue was softest, facilitating the organ’s removal."
"After learning how to bursectomize chickens, we then focused our attention on how to raise them and keep them alive outside when they were in such a fragile state. At the institute we established a clean room with filtered air and individual cages where we raised the chickens after they had been bursectomized. We then began to experiment with placing the chickens outside, as no one has ever experimented with taking bursectomized chickens out of a laboratory setting. We established that they were viable, and proceeded to design cages suitable to keep the chickens alive for the time they spent in the preselected environments. The greatest obstacle was heating, as chicks need to be kept at 80 – 90˚F during their first weeks. We collaborated with engineers and local technicians before arriving at the brilliantly simple solution of using a candle. We tried out dozens of candles before finding graveyard candles that burned for 5-days straight."
"Once all of this had been set in place, we were ready to put the chickens out in the environment. We conducted two trials, each involving 81 chickens, divided into 27 cages. We placed these cages in previously established transects of forest, farmland, and swamp. After five days in the field, the chickens were collected and blood samples were taken. I am unfortunately still waiting on the data, but the blood samples just arrived in the United States this week. They will be sent to a lab in UC Davis where they will be analyzed for pathogen load and acute phase proteins. This data will hopefully allow us to understand the spatio-temporal distribution of diseases in a patchy environment, in addition to a quantitative assessment of the stress placed upon each chicken’s immune system. If the data proves informative, a significant aspect of my thesis will be devoted to analyzing how the methodologies we developed may be employed in directing public health policies in different areas. For example, my collaborator already has plans to employ these methods in the tropics, to assess variability of pathogen virulence.

"Over the summer, I worked at the Center for the Study of the Presidency, an advocacy organization in the lobbying K St corridor of Washington. With the conclusions from our discussions in April and May in mind, I set out to better understand the politics behind HIV/AIDS. It was much sooner than I'd expected that I found myself knee-deep in data about the epidemic, shockingly not from abroad, but rather, from right under our nations' lawyers' noses in the District of Columbia. "
"I was riding the Washington Metro on my way home to Virginia when I noticed that I was staring at a public service announcement poster calling for more DC youths to get tested for HIV. The next morning, I was back in the office google-ing the project, and as soon as I discovered that 1 in 20 people live with the disease in the city, I told my boss, Dr. Susan Blumenthal, that I had come up with a research project for myself. She was more enthusiastic than I could have ever imagined, giving the amazing opportunity to publish my thoughts (under her name, with my name listed as the second author).
I could go into a lot of detail about what happened between then and the publication date because I gained a tremendous amount of very practical knowledge like developing better policy writing skills, how to communicate with no-nonsense government officials, how to communicate with nonsense government officials, etc. But, I'll stop there, and list my four big epiphanies from working on this project: 1) statistics and ethnography must be in equilibrium; 2) politics almost always make things messier and more confusing than needed; 3) community health programs are vital regardless of where you are, including the US; and 4) HIV/AIDS scientists are remarkably sanguine. "
"This op-ed only was about 25% of my summer, however. Another 25% was dedicated to investigating the Presidential hopefuls' health care plans, and particularly to how well they will deal with people with AIDS. In case you were wondering, it's indisputable that Barack Obama has a better plan than John McCain for HIV/AIDS patients (and if you ask me, for everything else except choice). Also, during this part of the summer, I spent some time helping a colleague write a policy brief on the status of AIDS in Asia. "
"I spent the third quarter working on the Palestinian Israeli Health Initiative, the health project that the Center was commissioned to investigate. This essentially was a large social experiment testing the validity of health diplomacy, or using health to bring people closer together. Not only did we have to do research for a report, but I spent a lot of time trying to create a WebMD/CDC.gov type site with health information for both Arabic and Hebrew speaking populations."
"The last 25% of the summer was spent researching tobacco, specifically concerning the possible FDA regulation of the substance. Dr. Blumenthal asked me to write another op-ed, but it hasn't been published yet. Look out for it in October or November. "

Trajectories of Medical Technology Distribution: A Comparative Ethnographic Study of Deworming Campaigns in Ghana and Belize

Organization/Location:

Princeton University

Adviser(s):

João Biehl

I am interested in the cultural dimensions of infectious disease, and my project combines ethnographic and archival research on the newly created category of "neglected tropical diseases." This new emphasis in health policy began to affect both Ghana and Belize very directly in 2006, when they each began to widely distribute pharmaceuticals as part of new National Deworming Campaigns. The comparative nature of this study is intended to emphasize the distinct social factors that come into play in the local reception of health policy, by tracking essentially parallel programs in the contexts of two former British colonies."
"While several anti-parasitic drugs (now donated by pharmaceutical corporations Merck and Glaxo-Smith Kline, respectively) are temporarily effective in combating intestinal parasites, local adults often hold their own beliefs regarding what causes such visible intestinal worm infections and how they are best cured. I am interested in exploring how pharmaceutical treatments are being received in such areas, and what lessons any conflicting beliefs or cultural tensions that emerge might hold for tropical health policy more broadly. How do international funding and global media attention play a role in shaping programs and the treatment resources available to community doctors and local families, or inflect their experiences of disease? My project explores the way that local perceptions of technology and medical need can dramatically affect the ways health programs are received-with the ultimate aim of illuminating both the intricacies of intercultural relations, and the life -shaping ways this knowledge might one day inform more culturally nuanced health policies.

“Increasing access to antiretroviral drugs (ARVs) has been a hard-fought battle made possible by unprecedented alliances among AIDS activists, governments, philanthropic and international agencies, and the pharmaceutical industry. Many public- and private-sector treatment initiatives are being launched worldwide, raising a whole new set of national and global healthcare policy challenges regarding adequate drug delivery, sustainable treatment access, and the integration of treatment with prevention. Broader questions arise as well: How can international institutions hold donors and partners accountable in the long term? In what ways can national governments stay involved (or increase their involvement) in ARV rollout? How does the variability of care infrastructure and treatment adherence affect drug resistance? And what effects do all of these issues have on the experience of living with HIV/AIDS and poverty on the ground?" (Joao Biehl)
"I specifically picked the topic of drug resistance to first line treatments and the access (or lack thereof) to patent protected treatment in Uganda. I had originally planned on looking into initiatives being taken to deal with drug resistance and also the distributions of ARVs in Uganda. However, on reaching Kampala, Uganda, with reading literature and talking to various health professionals, I changed my topic and started to focus on the issues surrounding treatment failure and decision making process of when to switch a patient from 1st to 2nd and line treatment. Faced with varying thresholds of measurement, definitions of treatment failure, limited switching options and issues of cost effectiveness, it was enlightening to learn how different treatment centers are dealing with this in an effort to provide the most efficient health care to those who need it. So I went around Kampala, the capital city, talking to different organizations including church organized AIDS programs, some government owned treatment centers, hospitals, NGOs etc talking to varying health professionals ranging from nurses, treatment dispensers to some administrators, trying to get understand what was happening with this issue of drug switching."
"From the different answers from different centers, the question of effectiveness/success of the Ugandan ART in absence of efficient monitoring strategies is raised. How best can this success be monitored? If patients are switched too late how will this affect the clinical success of 2nd line? Is a set of national guidelines and thresholds needed for health professionals to follow in order to have early detections? If so, how will the thresholds be determined, given the limited switching options available in resource limited settings? Given that a lot of these issues come up as a result of lack of switching options, the question lingers about whether it should be acceptable that resource limited settings should settle for just 2 regimens yet there exist 3rd and 4th line regimens in the Western world that have just been made available/accessible to this side of the world. It was a very amazing project that i would like to continue to do even this upcoming year."

Based on the most recent Nigeria Demographic Health Survey (DHS) in 2003, bed net usage is much lower in urban areas than in rural areas. This trend is the opposite of what is found in most other malaria endemic African nations. The objective of this research project was to discover why this was the case and how this trend could be reversed.

The search for a new tuberculosis drug: targeting the Mycobacterium tuberculosis malate synthase

Organization/Location:

Princeton University

Adviser(s):

Dr. Joel Freundlich/ Prof. Erik Sorensen

My research started with the synthesis and chemical analysis of various analogs of phenyldiketoacids (PKBAs). Upon successful synthesis and characterization, I submit the compounds to collaborators at the Texas A&M University for testing of the inhibitory activity of the compounds in malate synthase enzyme and M. tuberculosis whole-cell assays. Compounds showing high inhibition of the malate synthase in both assays will be further tested in animal models. The goal is to make appropriate modifications to the parent compound in order to increase its inhibitory activity against the enzyme. The finding if a highly potent analog will ultimately lead to the filing for patent rights to the compound and an ultimate development of the compound into a new drug for tuberculosis. This research should be useful in helping solve the current problem of increasing tuberculosis that the world faces. In a broad scientific perspective, the research will also contribute enormously to the understanding of disease-causing microorganism, their mechanism of persistence and adaptations that ultimately help these pathogens develop resistance to medications. Such an understanding will help combat microorganism resistance to antibiotics and pave a way for a breakthrough against pathogenic diseases.

To my extreme delight, I was chosen by the Grand Challenges Program of Princeton to be a research intern this summer in South Africa. The aim of the project was to study the connection between infectious disease priorities at the local government level and public health policies. The internship was sponsored by the Grand Challenges Global Health Initiative of Princeton University. As an intern, I (along with a team of three other students) was responsible for setting up and dialoging over 100 total interviews with elected officials of the Western and Eastern Capes to gauge how they prioritize challenges (especially those relating to health) that are faced by their constituency. I learned to remain focused and alert during our sometimes 12 hour work days. I learned to coordinate schedules with my research mates so that we could always travel in small teams for greater safety. I also learned how to upload data into online web portals and make analyses using excel programs. Although my Mondays-Fridays were normally devoted to interviewing and data entry, I also set up my own interviews with clinic administrators, doctors, and activists to create a body of knowledge for my own Honor's Thesis. My thesis will focus on the causes of stigma variance and its importance in a cross-regional context--an interest that was strengthened as an intern. I am so grateful for this amazing opportunity and have told so many people to connect with this Initiative to help uncover some of the most pressing challenges this world is facing.

Me and a group of three other students traveled to the Eastern and Western Capes of South Africa administering a standard survey derived by Professor Lieberman to various local government officials including municipal councilors, mayors, and municipal managers. The survey contained a series of questions that provided insight into how local officials prioritize issues facing their citizenry. Over the course of two months we were able to conduct a total of 117 interviews. All of the interviews were conducted in person.

"Current antiviral drugs work through one of the five following strategies 1) by blocking viral attachment to the host cell, 2) by disrupting replication of viral DNA/RNA, 3) by halting transcription of viral DNA or translation of viral mRNA, 4) or by preventing viral release from the host cell. However no antiviral drug yet takes advantage of the fact that viruses are almost completely dependent on host cell enzymes to produce key precursors for their growth, such as lipids for viral envelopes or amino acids for viral proteins."
"Drugs that inhibit specific human metabolic enzymes, such as statin drugs and methotrexate, have long been used as effective therapies for high cholesterol and leukemia respectively. Their success demonstrates that regardless of the cause of an illness, many diseases can be effectively managed at the level of metabolism. We assert that viral infections too may be viewed and treated, in part, as metabolic disorders. Inhibiting host-cell enzymes critical to virus replication is a promising new way to approach antiviral drug treatment. The difficulty however is to determine which specific enzymes in the set of over three-thousand known reactions in the human metabolism are critical to virus replication. However, not all the metabolic fluxes can be quantified through direct measurement, and those that cannot must be estimated in other ways. Flux balance analysis (FBA) is a computational technique used to predict the optimal capabilities of large-scale networks at steady state. It has been used, for example, to accurately predict the growth rate of a E. coli culture and the viability of E. coli gene knockouts.
"Flux balance analysis on the entire human metabolism is a new, unexplored, area. In 2006, Duarte et al. presented a global reconstruction of the human metabolism based on information from genomic data and published literature. To date it is the most comprehensive data set of its kind.
In my summer work, I apply FBA to the human model in an attempt to quantify the effect of human cytomegalovirus (HCMV) infection on host cell metabolic fluxes. Ichoose to study HCMV because of the large amount of transcriptional and metabolomic data available to our group that can be used to verify predictions made by the flux balance model. However the method described may be applied to any virus given an accurate description of its chemical composition."
"I use FBA to answer the following questions: Given a set of experimentally observed fluxes into and out of a host cell, what is the maximum number virus particles that can be produced? What single and double-knockouts of the host-cell enzymes will halt viral replication? What specific reactions are upregulated during viral replication compared to a mock infected cell? Enzymes catalyzing reactions that are both critical and upregulated comprise a promising set of antiviral drug targets. Thanks, huge thanks, to the Grand Challenges in Health for funding my summer work!"

"Iron is essential to life. All living organisms, including microbes, require iron to live and their ability to acquire iron is extremely important. My internship was focused on researching a mechanism of iron acquisition utilized by bacteria and fungi. Bacteria and fungi can produce molecules called siderophores when they are low on iron. They send the siderophores out into the environment, where they bind to iron. The microbes can then take up the iron-bound siderophores as a source of iron. Siderophores are essential for bacteria living in low iron environments, such as when they are infecting people. The ability to acquire iron is essential for the survival and virulence of the bacteria, and this mechanism is used by such bacteria as the ones that cause pneumonia and tuberculosis."
"My research studied the mechanism of how one specific siderophore, acinetoferrin, acquired iron from a human iron transport protein, transferrin. Transferrin is the primary iron transport molecule in humans, and could provide a source of iron for infecting bacteria. Discovering the mechanism of siderophore iron acquisition could provide insight in combating bacterial infections and provide a novel way of dealing with antibiotic-resistant strains."
"Our main approach to studying the siderophore was studying the interaction between transferrin and an analogue of the siderophore. Our hypothesis is that the siderophore displaces a synergistic anion in the protein iron-binding site, then chelates the iron and escapes the binding site by undergoing a conformational change. Our analogue in theory should be able to displace the anion, but lacks the necessary residues to chelate the iron completely. If we can see the analogue complexed with the iron in the protein binding site, then it supports our hypothesis that the first step for iron acquisition is displacement of the anion. We tested this by attempting to iron-load transferrin with the analogue and analyzing the protein with gel electrophoresis and UV-vis spectroscopy. Additionally, we are attempting to use mass spectrometry to find the product of a photochemical reaction of the analogue when it is complexed with iron. Future work also involves studying another analogue."

Climate and Energy

"During the summer of 2008, I worked with the Tuba City Regional Business Development Office (TCRBDO) on the Navajo Nation. The office, which is part of the Navajo Nation Department of Economic Development, helps facilitate local businesses on the reservation. Specifically, the office helps individuals write business plans, apply for Navajo Nation small business loans, and navigate through the business site leasing process. Furthermore, the office assists in communities in planning economic development projects."
"I spent much of my time soliciting contracts for land surveys, environmental assessments, and archaeological assessments—all of which are required before a business site lease is approved. Also, I worked with community leaders in business site development, assisted clients working on getting loans and business site leases, and compiled a summary document of the economic development plans for each community under our jurisdiction."
"Through working with the TCRBDO, I learned a lot about the challenges to economic development on reservation. The lack of private property is probably the most significant hurdle, as individuals must navigate a complicated bureaucracy in order to start a business. This process can sometimes take up to 5 years. A lack of business-related education also impedes local Navajo from starting effective businesses, along with a lack of credit. The TCRBDO periodically holds business-related training sessions in order to counteract this problem. However, clearly more is needed. Also, a lack of infrastructure makes starting business a costly endeavor, as often the entrepreneur has to invest in the costs of infrastructure to a potential business site. Finally, poor leadership and a complicated bureaucracy work to slow economic development projects on the reservation."
"In terms of energy development, my office was working with one company in particular to bring a wind farm to the reservation. It was the most promising renewable energy project on the reservations with plans for it to be fully operational by 2012. However, after spending my first two weeks of the summer working with the Navajo-Hopi Land Commission, it became clear to us that solar-based renewable energy projects hold the most promise on the reservation (see Tom Yersak’s Internship Summary for more details)."
One of the coolest developments I was a part of was the transfer of control of the business site leasing process from the Navajo government to a local community—the Shonto Chapter. This transfer will greatly decrease the time needed to start a local business, freeing the people from a government apparatus that hinders growth. My office was closely assisting Shonto Chapter, in order to make the transition as smooth as possible. Apparently, this is the first time a local government has been in control of the leasing process among any native peoples in the United States, and I had the privilege of attending the ceremony where the Navajo Nation officially transferred power to Shonto."
"Overall, I had an eye-opening, provocative summer. I learned a lot about the Navajo people and the challenges they face, while also enjoying the beauties of the American Southwest. The work may not have been the most stimulating, but I do believe that I did a small part to aid economic development on the reservation."

"The purpose of this project was to investigate and analyze a novel biofuel production system. I worked with a team of undergraduates, graduates, and professors to determine, both analytically and experimentally, the feasibility of such a system and its potential effects on the nation’s energy supply and total Carbon emissions."
"Like any alternative energy research, our project was motivated by a hope to see low-cost, non-polluting, domestically produced energy sources in the near future. Biofuels have long been held as a solution to our energy woes, but are plagued by a variety of their own troubles. While corn and other crops are traditionally considered as biofuel feedstock, algae offer a promising future as an alternative feedstock. Algae provide a simple solution to the food competition problem. Namely, algae do not compete for growing space with food crops. Algae are grown primarily in oceanic environments or man-made aquatic environments, neither of which will use available agricultural space. At the same time, algae have productivity rates (growth rates) that can exceed terrestrial plants’ productivity rates by up to ten-fold. In other words, given the same amount of sunlight, algae can produce ten times as much biomass (and therefore ten times as much fuel) as a typical terrestrial crop like corn or Elephant Grass."
"In order to quantify the potential economic and climate benefits of adopting an algae-based energy production scheme, our team modeled a full-length production system and calculated costs along each step of the system. The basic system was divided into several key components: namely, Algae Growth, Algae Harvest, Conversion to Biogas, Biogas Cleanup, and Pipeline Connections. Each of these modules was thoroughly researched using available scientific literature and industrial contacts. Our model demonstrated two primary results. The first significant results were that an algae-based natural gas system would be almost entirely dependent on the price of sewage sludge. In our model, we assumed that a tipping fee is provided for the removal of sewage sludge. This tipping fee was the most significant added value in our system and vastly outweighed the value of the actual fuel generated or any Carbon credits accrued. As a result, our system was economic only while scaled to the size of the sewage waste market. This market, while large, would only allow an energy generation system equivalent to about 1% of the U.S. energy market. Our second primary result was the inherent uneconomical nature of the system. Using relatively conservative assumptions, we determined that the costs of gathering and transporting algal biomass far outweighed the biomass’ value as a fuel source. As mentioned before, the system only proved economical when a major adjunct service (sewage removal) was provided as well."

Nuclear fission plants provide a stable and powerful source of energy, capable of producing large amounts of electricity compared to the size of the facility. However, fission plants suffer from the side effect of producing dangerous and extremely long-lasting radioactive waste in the process as well as posing a small risk of an uncontrolled reaction leading to an explosion. Nuclear fusion reactors are meant to remedy these most troublesome issues of current nuclear plants. When isotopes of hydrogen are combined to produce helium in fusion reactors, only small amounts of radioactive material is produced as the reactor components become activated. Furthermore, only small amounts of hydrogen are in the reactor at any given time so even an uncontrolled fusion chain reaction would not produce energy at dangerous rates."
"The specific aim of my project was to model the so-called Neutral Beam Injectors (NBI) used in tokamak fusion reactors for heating up the hydrogen plasma. During the project I wrote a piece of software that reads in parameters describing an NBI system and produces a random sample of ionized particles from the neutral particle beam. Initially I spent a significant amount of time reading scientific papers about the topic in order to familiarize myself with plasma physics and, in particular, to find a good method for calculating the ionization rates inside the plasma. During the rest of the summer my time was taken almost entirely by implementation of the algorithm in Fortran code, and by data collection of the geometric parameters of the NBI system used in various tokamaks, such as ITER, JET, and AUG.
Overall, the internship was a great experience. The end result of the project was a simple but well-tested and functional module that can be used to create initialization data for programs that simulate what happens to the particles once they are ionized. I also enjoyed the atmosphere and excitement about fusion at the lab, so the experience certainly made me give more serious though to the possibility of returning to Finland to study fusion after graduating from Princeton.

"I spent this summer helping Professor Stephen Schneider of Stanford University in Stanford, California. Since Professor Schneider was often away traveling I spent the majority of my time working with Dr. Michael Mastrandrea. Professor Schneider and Dr. Mastrandrea have been working together for several years studying issues surrounding climate change. The scope of my work focused on two projects that Dr. Mastrandrea had begun to work on: Future Greenhouse Gas Emissions Scenarios and Extreme Events in California."
"We worked to make a report on future GHG emissions using probabilistic projections of the emissions and radiative forcing pathways. This could be used to help model future climate in California. The probabilistic projections for the report were based on both existing scholarly research and a new survey of expert opinion."
"The goal of the second project was to improve existing research on the end-user impacts of extreme events in California. The report focused on the assessment of present and future changes to end-users in the likelihood of events similar in magnitude to historical events. The report also looks at the likelihood of future extreme events and events more intense than those observed in the past."

In order to address the dual threats of climate change and energy security, I endeavored to develop a novel energy production system utilizing anaerobic biodigestion of the abundant, pelagic macroalgae, Sargassum Fluitans. I worked at Princeton, together with a team of undergraduates, to analyze this novel technology, focusing on conversion pathways and nutrient provision.

A Plasma Spark plug (PSP), like conventional electric spark plugs, produces a source to ignite fuel. However unlike electric spark plugs, the source is essentially a different state of matter, with a larger surface area to ignite fuel. This increased surface area leads to a greater efficiency of an ordinary combustion engine, reducing the volume of fuel used.
The summer project involved two main components; a practical training aspect with the electrical firing circuit-in order to get acquainted to the system. The second, more important component was to produce an effective computer simulation of the firing circuit. This was so that several configurations of circuits could be tested with speed and that anomalies could easily be evaluated and corrected within the circuit. PSP has the potential to be very useful in several different types of combustion engines, with the airplane engine being of particular interest. In addition, in a time of high fuel prices, the need for inventions like PSP can be very beneficial.

MIRTHE (Mid-Infrared Technologies for Health and the Environment) Center at Princeton University; and Institute for Atmospheric Physics at the Chinese Academy of Sciences in Beijing, China

Adviser(s):

James A. Smith

"The primary purpose of this project was to investigate the various effects of urbanization (the urban heat island, the urban canopy, and urban aerosols) on rainfall climatology, with a special focus on Beijing. A group of students, researchers, and faculty of the MIRTHE (Mid-Infrared Technologies for Health and the Environment) Center at Princeton University collaborated with scientists at the Institute for Atmospheric Physics at the Chinese Academy of Sciences on this project. Over the course of the summer of 2008, a multifaceted approach was taken to assess urban impacts on Beijing rainfall climatology. Components of the Beijing 2008 summer climatology project included air quality monitoring, meteorological data collection, atmospheric modeling, and review of Chinese-language literature. The administrative restrictions placed on Beijing air pollution as part of the 2008 Beijing Summer Olympics provided a unique setting for studying the effect of abrupt changes in air pollutant emissions on air quality and meteorology."
"The focus of my work was on the meteorological modeling (using the Weather Research and Forecasting (WRF) model) and on review of the Chinese language literature regarding urbanization effects on summer meteorology in Beijing. WRF model sensitivity analyses of severe summer rainfall events in Beijing indicated the important effects of spin-up time and domain/grid scheme on model results. Review of Chinese language literature found that strong orographic influences and the short-duration, localized nature of thunderstorms indeed makes modeling of summer rainfall very difficult. These findings about model sensitivity will hopefully inform future efforts to study the effects on urbanization on precipitation in Beijing."

"As an ACORE intern from June to September 2008, I had the opportunity to both provide valuable program support for full-time ACORE staff and conduct my own personal research."
"Specifically, I compiled a list of over 200 contacts in the energy/renewable energy/environmental practices of several law firms throughout the U.S. for recruitment for ACORE's American Bar Association (ABA) Teleconference Series, a monthly webinar convening energy lawyers, business experts and policymakers. In addition to research support for ACORE's new International Committee (currently with a specific focus on China) and some website development, I provided research support for ACORE's National Governors Association (NGA) 50 States project, which was presented to the NGA National Resources Committee in July 2008."
"Complimenting my semester abroad junior independent research on the Clean Development Mechanism in South Africa, my personal research included a critical summary of South Africa's renewable energy policies and technologies as well as an overview of the proposed International Renewable Energy Agency (IRENA) and the activities of other international institutions working in the field of renewable energy."
"Overall, my internship provided me with the ideal opportunity to better understand the interfaces between trade, finance, law and policy in renewable energy development, relationships which will become increasingly apparent and essential both in the U.S. and throughout the world in the years ahead."

In order to address the dual threats of climate change and energy security, I endeavored to develop a novel energy production system utilizing anaerobic biodigestion of the abundant, pelagic macroalgae, Sargassum Fluitans. I worked at Princeton, together with a team of undergraduates, to analyze this novel technology, focusing on conversion pathways and nutrient provision.

MIRTHE (Mid-Infrared Technologies for Health and the Environment) Center at Princeton University; and Institute for Atmospheric Physics at the Chinese Academy of Sciences in Beijing, China

Adviser(s):

Claire Gmachl, Gerard Wysocki, and James A. Smith

The summer of 2008 promised to be a momentous period in history. In particular, the world watched with bated breath as China, the emerging power drew up elaborate plans for the Olympics in August. The sports extravaganza drew athletes, sports fans, tourists, businessmen – and scientists! When Beijing was named the host city, the idea of organizing a clean and green Olympics was a central theme. However several months preceding the Games, environmental concerns, specifically, air quality and pollution, came to the fore. The authorities adopted radical measures including shutting down or relocating polluting industrial units and taking several vehicles off the roads. For scientists this presented a unique and large-scale experimental platform to understand Beijing climatology.
At the Mid-Infra Red Technologies for the Health and Environment (MIRTHE), an NSF Center at Princeton, researchers from Civil and Environmental Engineering and Electrical Engineering pooled together their expertise to study the regional environment. We partnered with the Institute of Atmospheric Physics, Chinese Academy of Sciences to carry out our studies. One aspect of the project included employing WRF-Chem, the Weather Research and Forecasting Model, to simulate weather patterns, while incorporating pollution data. I worked with the group on another component of the project that involved developing and deploying novel mid-infra-red spectroscopic equipment. The mid infra-red region of the spectrum is special because it contains strong absorption lines of several gaseous pollutants. The Quantum Cascade Laser Open Path System (QCLOPS) is an open path sensing system that analyzes the retro-reflected laser light to monitor ozone, ammonia, and carbon dioxide. The Nitric Oxide point sensor system is based on the principles of Faraday rotation spectroscopy resulting in sub-parts-per billion sensitivity. It was exciting learning about the instruments, while exploring techniques for studying and analyzing the data. Further, it was an enriching experience working in China, especially during the Olympics and provided a great insight into the culture, ethos, and systems of the nation.

"ISLES, a Trenton-based nonprofit community development organization, is looking to help the Trenton community and create employment opportunities by developing a program to audit and retrofit homes in the city. Low-income households use significantly more energy per square foot than high-income homes, almost completely due to waste and inefficiency."
"Much of my time was spent researching existing programs throughout New Jersey, the US, and the world, and attempting to find the role, which would best suit Isles. I also looked into cost effective strategies for retrofits, as well as advocacy for possible changes to current state policy. Isles' program will be very effective at addressing issues of climate change as well as urban poverty, through both lower energy bills and the creation of green-collar jobs."

I worked for the Navajo Hopi Land Commission Office with two Navajo Princeton Alums: Roman Bitsuie ’79 and Larry Nez ’81. NHLCO is charged with acquiring and developing “New Lands” for the benefit of Navajo relocatees affected by land disputes. The executive director of the NHLCO, Roman Bitsuie, is interested in developing large-scale solar projects on the New Lands to create new jobs and revenue for the Navajo Nation. With a 50% unemployment rate on the reservation, jobs and funds for assistance are the most valuable benefits the NHLCO can provide relocatees. Such projects are also very popular on the Reservation given the negative environmental impacts of several coal strip mines and power plants in the surrounding area.
Everyday I was exposed to the issues involved with getting large-scale renewable energy projects off the ground. My internship focused mainly on the initial research for a land survey and an environmental impact statement (EIS) needed for approval of any large-scale construction project. I was also involved in the day-to-day operations of the office.